Proton pump inhibitor use and risk of hip fractures among community‐dwelling persons with Alzheimer's disease—a nested case‐control study

Abstract

Summary Background Hip fractures are a major health concern among older persons with Alzheimer's disease, who usually use many concomitant drugs for several diseases. Evidence of the association between proton pump inhibitor use and risk of hip fracture is contradictory. Aim To investigate whether the long‐term use of proton pump inhibitor is associated with risk of hip fractures among community‐dwelling persons with Alzheimer's disease. Methods In this nested case‐control study, the nationwide MEDALZ data were utilised. Community‐dwelling persons with Alzheimer's disease who encountered incident hip fracture (N = 4818; mean age 84.1) were included as cases. Four controls were matched for each case at the date of hip fracture (N = 19 235; mean age 84.0). The association between hip fracture and duration of current PPI use (ongoing use during 0‐30 days before the index date), and cumulative duration of use during 10 years before was investigated with conditional logistic regression. Results Long‐term or cumulative proton pump inhibitor use was not associated with an increased risk of hip fracture. Current proton pump inhibitor use was associated with an increased risk of hip fracture (adjusted OR 1.12, 95% CI 1.03‐1.22). The risk was increased in short‐term current use (<1 year) (adjusted OR 1.23, 95% CI 1.10‐1.37). Conclusions The increased risk of hip fracture was evident only in short‐term proton pump inhibitor use, but no association was found for long‐term or cumulative use. Thus, our findings do not support previous assumptions that long‐term proton pump inhibitor use would be associated with an increased risk of hip fractures.

Monitoring the growing use of esomeprazole

“…[1][2][3][4] It is important to acknowledge that much of the evidence comes from observational studies and only suggests associations, rather than proves cause and effect, and there are studies that cast doubt on the validity of the concerns. 5,6 However, even commentators who question the validity of the link between PPIs and such adverse effects continue to suggest that PPIs should be used at the lowest effective dose, and…”

Letter: association between proton pump inhibitor use and fracture risk ‐ causality or confounding?

“…Second, the study population comprised patients with Alzheimer's disease, which is itself is a risk factor for hip fracture due to unclear reasons. 8,9 In addition, since the patients were community dwelling, future studies among institutionalised persons are needed. Therefore, whether the results apply to the general population is a problem.…”

Editorial: let's take a break from studying the PPI‐fracture association—Authors’ reply

“…We thank Dr. Targownik for her interest in our article . She raised important points in her invited editorial.…”

“…As pointed out in the discussion section, it is unlikely that the association between PPI use and hip fracture is causal. The main reason for hip fractures among persons with Alzheimer's disease is falling, not osteoporosis.…”